CausalSentinel

Protein Dossier — GZMM (Granzyme M)

MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).

1. Published MR estimates (retrieved, not computed)

Outcome beta se p method nSNP cis/trans coloc
Neuroticism 0.0395 0.0186 0.0336 Wald ratio 1 cis NA
Non-cancer illness code self-reported: uterine fibroids -0.244 0.119 0.041 Wald ratio 1 cis NA
Rheumatoid arthritis -0.577 0.293 0.0488 Wald ratio 1 cis NA
Diagnoses - main ICD10: N81 Female genital prolapse 0.152 0.0823 0.0651 Wald ratio 1 cis NA
Diagnoses - main ICD10: M23 Internal derangement of knee -0.155 0.0901 0.0865 Wald ratio 1 cis NA
Diagnoses - main ICD10: K43 Ventral hernia 0.236 0.138 0.0871 Wald ratio 1 cis NA
Fractured bone site(s): Ankle 0.144 0.0848 0.0897 Wald ratio 1 cis NA
Invasive mucinous ovarian cancer -0.312 0.186 0.0929 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol 0.049 0.0293 0.0945 Wald ratio 1 cis NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities -0.144 0.0927 0.119 Wald ratio 1 cis NA
Depressive symptoms 0.0325 0.0209 0.12 Wald ratio 1 cis NA
Diagnoses - main ICD10: G47 Sleep disorders -0.338 0.221 0.125 Wald ratio 1 cis NA
…and 53 more outcomes (see JSON)              

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

3. GWAS Catalog results — traits with signal at this locus

4 association rows across 4 traits (1 genome-wide significant rows). Associations are loci, not causal claims; the mapped gene at a locus is not necessarily the effector gene.

Trait best p lead SNP n assoc study MR status
Total protein levels x insomnia interaction 1e-10 rs76360971 1 GCST90026658 no MR -> candidate analysis
Gut microbial network clusters (Salmon (at 1 year) x Househo 1e-7 rs6510836 1 GCST90569455 no MR -> candidate analysis
Gut microbial network clusters (Salmon (at 1 year) x Househo 2e-7 rs6510836 1 GCST90569451 no MR -> candidate analysis
Response to antidepressants (symptom improvement) in major d 5e-6 rs111763479 1 GCST90244558 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 122 total). Associations are loci, not causal claims. The causal-status column is a four-state triage per pair: established (curated) = a curated clinical assertion exists (ClinGen/G2P/GEL/Orphanet/ClinVar — any validity level, MR adds little); exploratory rare-variant signal = ExWAS burden evidence without curation — a candidate NEW gene-disease relationship; common-variant locus = GWAS signal, classic pQTL-MR territory; multi-layer = burden+GWAS together, an allelic-series candidate (the strongest causal setup). Burden estimand is carrier-vs-noncarrier, not per-SD MR.

Disease genetic assoc. burden (ExWAS) causal status MR status
tooth disorder 0.359 common-variant locus no MR -> candidate analysis
insomnia 0.042 common-variant locus no MR -> candidate analysis

Of the 2 rows above, 2 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 0 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.

5. Downstream annotation (druggability & safety preview)

Layer Result
ChEMBL druggability 0 known modulators (Granzyme M)
gnomAD constraint pLI=1.1e-09, LOEUF=1.69 — LoF-tolerant
GWAS Catalog 32 unique SNPs / 64 rows
ClinVar 89 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance